The present invention pertains to a composition for inducing a pattern of gut barrier maturation similar to that observed with breast feeding and able to improve gut barrier maturation, e.g. during neonatal stress. In particular, the present invention relates to an infant formula containing a combination of specific ingredients designed to provide a synergistic effect all along gastrointestinal tract and barrier function.
During the postnatal development, the newborn intestine experiences a process of maturation that ends by the establishment of a functional barrier to macromolecules and pathogenic bacteria. This phenomenon is called gut closure and appears to be affected by the diet. Hence, different studies with infants (JPGN, 1995, 21: 383-6) and animal models (Pediatr Res, 1990, 28: 31-7) show that the maturation of the barrier is faster in breast-fed than in formula-fed newborns. This could explain the higher prevalence of allergy and infection in infants fed formula than in those fed with mother milk.
An impressive number of different mechanisms integrate this barrier, mechanisms that act synergistically to protect the host from the luminal aggressions. The first barrier consists on the intestinal epithelium, a continuous monolayer of columnar epithelial cells sealed together by protein complexes, such as the tight junctions. The second is a non-specific barrier composed by mechanisms that protect the mucosal surface as saliva, gastric acidity, mucus layer, proteolytic digestion, alkaline intestinal pH, unstirred layer and intestinal peristalsis. The gut immune system (GALT) is able to respond selectively and specifically to the foreign molecules and pathogen microorganisms. Finally, and not less important, intestinal flora directly and indirectly protect against host invasion by pathogens and macromolecules with antigenic properties.
Moreover, physical stress due for instance to antibiotherapy, disease or surgery and psychological stress induced for instance by hospitalization or prolonged separation from the mother, common situations in the preterm infant population, may impair further the maturation of the intestinal barrier and delay closure. Therefore, microbial flora has shown to affect the status of various mechanisms of the intestinal barrier (mucus layer, tight junctions) and both physical and psychological stress has been related to increased permeability to macromolecules, small solutes and bacteria.
In the art several means have been proposed to improve gut barrier function or gastrointestinal health in infants. For example, in U.S. Pat. No. 6,132,710, purified Lactobacillus salivarius and Lactobacillus plantarum strains are administered to preterm infants to prevent injury caused by infection and inflammation to mucosal tissue, especially by nasogastric administration to prevent gastrointestinal tissue injury in neonatal necrotizing enterocolitis.
Also, JP 5030942 provides a food and drink containing active component of milk fat globule membrane (MFGM), which can control permeability of high molecular substances, such as protein, through intestine vessel. It is useful for prevention and therapy of food allergic disease.
As regards to gut barrier immunity, WO 9700078 provides a protein hydrolysate for down-regulating hypersensitivity reactions and for promoting the gut immune barrier, which is made by hydrolyzing proteins with: (a) enzymes derived from a preparation containing probiotic gastrointestinal bacteria and (ii) a protease system similar to that of Lactobacillus GG and (b) pepsin and/or trypsin.
Though those microorganisms or ingredients bring about a great potential of beneficial effects for the individual incorporating them, a disadvantage resides in that said microorganisms or ingredients only exert their effect in limited parts of the intestine and on individual mechanisms of the intestinal barrier.
Therefore, an object of the present invention resides in obviating the disadvantages of the prior art and providing improved means to promote simultaneous maturation of various mechanisms of the gut barrier and this all along the intestine during formula feeding, in order to induce a pattern of gut barrier maturation similar to that observed with breast-feeding.